Identification of an arene oxide metabolite of 2,2',5-5'-tetrachlorobiphenyl by gas chromatography-mass spectroscopy.
Tritiated 2,2'5,5'-tetrachlorobiphenyl (3H-TCB) was incubated with phenobarbital(PB)-induced rat liver microsomes in the presence of an epoxide hydrase inhibitor and brominated analog (BrAO) of the expected metabolic intermediate, 2,2',5,5'-tetrachlorobiphenyl-3,4-oxide (TCBAO). A putative arene oxide intermediate (3H-AO), which was radiolabeled, was separated from 3H-TCB and  BrAO by column chromatography, high pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC), and was analyzed for TCBAO by methods that were independent of radiometric techniques. The retention times (Rt's) of TCBAO and 3H-AO on two gas chromatography (GC) columns were the same, both before and after acid catalyzed rearrangement. 3H-AO was further characterized by rearrangement to a mixture of 3- and 4-hydroxy-TCB that was identified by gas chromatography-mass spectroscopy (GC-MS). The rate of TCB metabolism and the production of 3H-AO by liver microsomes from a PB-induced, adult male rhesus monkey was less than that observed with rat microsomes. The 3H-AO from the monkey was also characterized as TCBAO by rearrangement to the characteristic TCB phenols that were analyzed by GC-MS using selective ion monitoring. This study is the first in which an arene oxide of a polychlorinated biphenyl (PCB) was actually isolated as a mammalian metabolite and subjected to direct chemical analysis.
D000818:Animals; D001711:Biotransformation; D004852:Epoxy Compounds / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D066298:In Vitro Techniques; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; C009407:2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls; D010634:Phenobarbital